Prenatal diagnosis using combined quantitative fluorescent polymerase chain reaction and array comparative genomic...

First, to assess the performance of a prenatal diagnostic service using quantitative fluorescent polymerase chain reaction (QF-PCR) and array comparative genomic hybridization (aCGH) as first-line investigations. Second, to determine the incidence of copy number variants (CNVs) by indication for testing, with particular reference to ultrasound and biochemical parameters measured in combined first-trimester screening.

All patients undergoing invasive prenatal testing at a specialist prenatal screening service in Sydney, Australia, were included in the study. All samples underwent QF-PCR and targeted aCGH.

Of 1049 cases, CNVs were reported in 156 (14.9%). Preliminary QF-PCR identified abnormalities in 104 of these cases. Of the remaining 52 cases, 20 could have been detected on karyotype testing, leaving 32 cases (3.1%) with CNVs only detectable by aCGH, of which 13 (1.2%) were pathogenic. Variants of unknown significance (VOUS) were seen in only three cases. Fetal structural abnormalities identified in the first trimester were the group most likely to be associated with pathogenic CNVs (11.8%).

Combining QF-PCR and aCGH is an effective first-tier prenatal testing regime that does not require conventional karyotyping. The incidence of VOUS in this study was very low owing to appropriate aCGH targeting and specific reporting criteria that reduced the number of potentially difficult counseling encounters. Pathogenic CNVs are positively correlated with the presence of fetal structural abnormalities, but not with enlarged nuchal translucency or abnormal first-trimester serology results.